In the postgenomic era, the structures or functions of human proteins, which are sometimes said to be 100,000 or more types, are being elucidated, and many proteins that can become a component of a remedy for disease (drug proteins) have been identified. On the other hand, however, the fact is that the route of administration of a therapeutic protein is generally by way of injection only. Injection is considered rather appropriate during hospitalization or on a hospital visit in the acute phase of disease, however it is not easy to maintain blood concentration by injection administration in any case except for drip injection. Therefore, administration at a medical institute becomes a premise except for limited protein formulations and medical care cost becomes expensive compared with the case of oral administration. Further, in many cases using injection, stresses such as pain are unavoidable especially for such as pediatric patients. In addition, consecutive injection administration on consecutive days often involves with changes in tissues such as a hard lump around the injection site. Further, not a small amount of medical wastes such as containers for injection solution and injection syringes are produced and costs are incurred for such reasons. For these reasons, great expectation is placed on oral administration in the chronic phase of disease. Because of this, the methodology for absorption via oral mucosa or the methodology for covering, coating or the like with a chemical material to prevent digestion is coming to be used practically. However, in the present situation, an absorption rate in oral administration hardly exceeds 30% even in these methodologies in most cases. For example, Clement S. et al. reported the results of clinical trials by the oral administration of insulin (Phases I and II) and the absorption rate of insulin by oral administration is less than 30% (Clement S. et al. Metabolism. January 2004; 53(1): 54-58).
Nattokinase is an enzyme (protease) produced by Bacillus subtilis natto (Bacillus subtilis), and an invention utilizing its thrombolytic effect (e.g., JP-A-2002-360220) has been known. However, it is not known that this nattokinase highly efficiently realizes the transfer of a bioactive polypeptide from the digestive organs into the blood stream.